CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury

被引：281

作者：

Joy, Mary T. ^{[1
]}

Ben Assayag, Einor ^{[6
,8
]}

Shabashov-Stone, Dalia ^{[7
]}

Liraz-Zaltsman, Sigal ^{[7
,9
,10
]}

Mazzitelli, Jose ^{[1
]}

Arenas, Marcela ^{[1
]}

Abduljawad, Nora ^{[1
]}

Kliper, Efrat ^{[6
]}

Korczyn, Amos D. ^{[8
]}

Thareja, Nikita S. ^{[1
]}

Kesner, Efrat L. ^{[7
]}

Zhou, Miou ^{[2
,3
,4
,5
]}

Huang, Shan ^{[2
,3
,4
,5
]}

Silva, Tawnie K. ^{[2
,3
,4
,5
]}

Katz, Noomi ^{[10
]}

Bornstein, Natan M. ^{[6
,8
]}

Silva, Alcino J. ^{[2
,3
,4
,5
]}

Shohami, Esther ^{[7
]}

Carmichael, S. Thomas ^{[1
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Neurobiol, Integrat Ctr Learning & Memory, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Integrat Ctr Learning & Memory, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Dept Psychol, Integrat Ctr Learning & Memory, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA

[6] Tel Aviv Sourasky Med Ctr, Dept Neurol, Tel Aviv, Israel

[7] Hebrew Univ Jerusalem, Inst Drug Res, Dept Pharmacol, Jerusalem, Israel

[8] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel

[9] Sheba Med Ctr, Joseph Sagol Neurosci Ctr, Tel Hashomer, Israel

[10] Ono Acad Coll, Inst Hlth & Med Profess, Kiryat Ono, Israel

来源：

CELL | 2019年 / 176卷 / 05期

关键词：

CLOSED-HEAD INJURY; FUNCTIONAL RECOVERY; DENDRITIC SPINES; PREMOTOR CORTEX; PLASTICITY; REHABILITATION; MEMORY; AGE; REGENERATION; HEMIPARESIS;

D O I：

10.1016/j.cell.2019.01.044

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We tested a newly described molecular memory system, CCR5 signaling, for its role in recovery after stroke and traumatic brain injury (TBI). CCR5 is uniquely expressed in cortical neurons after stroke. Post-stroke neuronal knockdown of CCR5 in pre-motor cortex leads to early recovery of motor control. Recovery is associated with preservation of dendritic spines, new patterns of cortical projections to contralateral pre-motor cortex, and upregulation of CREB and DLK signaling. Administration of a clinically utilized FDA-approved CCR5 antagonist, devised for HIV treatment, produces similar effects on motor recovery post stroke and cognitive decline post TBI. Finally, in a large clinical cohort of stroke patients, carriers for a naturally occurring loss-of-function mutation in CCR5 (CCR5-Delta 32) exhibited greater recovery of neurological impairments and cognitive function. In summary, CCR5 is a translational target for neural repair in stroke and TBI and the first reported gene associated with enhanced recovery in human stroke.

引用

页码：1143 / +

页数：28

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